What are the side effects of Xeloda (capecitabine) and how are they managed?

Xeloda (Capecitabine) Side Effects and Management

Most Common Side Effects

Hand-foot syndrome is the most characteristic and frequent adverse effect of capecitabine, occurring in up to 73% of patients, with 11% experiencing grade 3 events requiring dose modifications or treatment interruptions. 1

Gastrointestinal Effects

• Diarrhea is extremely common, particularly when capecitabine is combined with other agents 2, 1
• Nausea, vomiting, and loss of appetite occur frequently 3
• Stomatitis (mouth and throat sores) affects many patients 3
• Abdominal pain, upset stomach, constipation, and dehydration are reported 3

Dermatologic Effects

• Hand-and-foot syndrome (palmar-plantar erythrodysesthesia) causes tingling, numbness, pain, swelling, or redness of palms and soles 3
• Rash, dry or itchy skin, and skin discoloration occur commonly 3
• Nail problems and hair loss (though less than with IV 5-FU) 4

Hematologic Effects

• Thrombocytopenia is especially common when combined with other agents 1
• Grade 3/4 neutropenia occurs in 6.3% of breast cancer patients 5
• Mild-moderate anemia and leukopenia affect 36.4% of patients 6
• Significantly lower incidence of grade 3/4 myelotoxicity compared to infusional 5-FU 7

Other Common Effects

• Fatigue, weakness, dizziness, and headache 3
• Fever, pain (chest, back, joint, muscle), trouble sleeping 3
• Taste problems 3

When to Stop Treatment Immediately

Contact your doctor immediately and stop taking capecitabine if you experience: 3

• Diarrhea: 4 or more additional bowel movements per day beyond baseline, or any nighttime diarrhea
• Vomiting: More than once in 24 hours
• Nausea: Severe loss of appetite with significantly reduced food intake
• Stomatitis: Pain, redness, swelling, or sores in mouth
• Hand-foot syndrome: Pain, swelling, or redness preventing normal activity
• Fever/infection: Temperature ≥100.5°F or signs of infection

Special Population Risks

Elderly Patients

• Patients over 65 years have significantly higher risk of severe toxicity (34% grade 3 or higher), including treatment-related deaths 1, 5
• Consider starting dose of 1,000 mg/m² twice daily in elderly patients 5
• All common side effects are more frequent in patients age 80 and older 3

Geographic Variation

• North American patients experience greater toxicity than European patients, warranting particularly careful observation 5
• A gradient of fluoropyrimidine toxicity exists: high in the US and low in East Asia 7

Patients with DPD Deficiency

• Patients with partial or complete DPD (dihydropyrimidine dehydrogenase) deficiency (3-5% of population) may experience potentially life-threatening toxicity 1, 3
• Do not take capecitabine if you have been told you lack the DPD enzyme 3

Renal Insufficiency

• Patients with kidney problems require dose adjustment since elimination is primarily renal 1, 3

Combination Therapy Considerations

With Docetaxel

• Higher incidence of hand-foot syndrome (25.2% vs 1.3% with gemcitabine/docetaxel) 1
• Increased nausea/vomiting (8% vs 3.4%) 1
• Increased mucositis (4.4% vs 1.3%) 1

With Neratinib

• Diarrhea is the most frequent side effect (any grade: 83%, grade 3/4: 24%) 2
• Grade 3 diarrhea occurred in 29% of patients in combination trials 2

Management Strategies

For Grade 1 Toxicity

• Continue treatment with close monitoring 1, 5

For Diarrhea Management

• Mild diarrhea: Loperamide 4 mg four times daily 1
• Persistent diarrhea (>1 week): Treat as grade 2 diarrhea 1
• Severe diarrhea: Loperamide every 2 hours; if no improvement after 24-48 hours, consider octreotide 100 μg three times daily 1
• Grade 3-4 diarrhea with neutropenia, fever, reduced oral intake, or concerning symptoms: Immediate hospitalization may be required 1

For Nausea/Vomiting

• For moderate emetogenic chemotherapy regimens: 5-HT-receptor antagonist (preferably palonosetron) plus dexamethasone 8 mg on day 1, followed by dexamethasone 8 mg on days 2-3 1

Dose Modifications

• Once dose has been reduced, it should not be increased at a later time 3
• Temporary interruptions and dose modifications do not reduce overall efficacy and will most likely lead to resolution of side effects 4
• Your doctor may stop treatment for a while or adjust the dose; if caught early, most side effects improve after stopping capecitabine 3
• If side effects do not improve within 2-3 days after stopping, call your doctor again 3

Critical Drug Interactions

Warfarin (Coumadin)

• Capecitabine may significantly increase the effect of warfarin, potentially leading to serious bleeding 3
• Your doctor needs to check blood clotting more often and adjust warfarin dose as needed 3

Phenytoin (Dilantin)

• Your doctor needs to test phenytoin blood levels more often or change the dose 3

Folic Acid

• May affect how capecitabine works 3

Monitoring Requirements

• Close monitoring during the first treatment cycle is essential, with particular attention to hand-foot syndrome, diarrhea, and coagulation parameters in those on anticoagulants 5
• Dose adjustments should be made as needed based on toxicity 5
• Patients may need liver function monitoring if they have liver problems 3

Important Contraindications

• Do not take if: nursing a baby, allergic to 5-fluorouracil or capecitabine, or lack the DPD enzyme 3
• Do not become pregnant while taking capecitabine; use effective birth control 3
• Men should use birth control while taking capecitabine 3